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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03786783




Registration number
NCT03786783
Ethics application status
Date submitted
24/12/2018
Date registered
25/12/2018
Date last updated
13/08/2019

Titles & IDs
Public title
Dinutuximab, Sargramostim, and Combination Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma Undergoing Stem Cell Transplant
Scientific title
A Pilot Induction Regimen Incorporating Chimeric 14.18 Antibody (ch14.18, Dinutuximab) (NSC# 764038) and Sargramostim (GM-CSF) for the Treatment of Newly Diagnosed High-Risk Neuroblastoma
Secondary ID [1] 0 0
NCI-2018-03732
Secondary ID [2] 0 0
NCI-2018-03732
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ganglioneuroblastoma 0 0
High-Risk Neuroblastoma 0 0
NMYC Gene Amplification 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Children's - Other
Cancer 0 0 0 0
Children's - Brain
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Aldesleukin
Treatment: Surgery - Autologous Hematopoietic Stem Cell Transplantation
Treatment: Drugs - Carboplatin
Treatment: Drugs - Cisplatin
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Dexrazoxane
Other interventions - Dinutuximab
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Etoposide
Treatment: Other - External Beam Radiation Therapy
Treatment: Drugs - Isotretinoin
Treatment: Drugs - Melphalan
Other interventions - Sargramostim
Treatment: Drugs - Thiotepa
Treatment: Drugs - Topotecan
Treatment: Drugs - Vincristine

Experimental: Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT) - See Detailed Description


Other interventions: Aldesleukin
Given IV

Treatment: Surgery: Autologous Hematopoietic Stem Cell Transplantation
Undergo ASCT

Treatment: Drugs: Carboplatin
Given IV

Treatment: Drugs: Cisplatin
Given IV

Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Drugs: Dexrazoxane
Given IV

Other interventions: Dinutuximab
Given IV

Treatment: Drugs: Doxorubicin
Given IV

Treatment: Drugs: Etoposide
Given IV

Treatment: Other: External Beam Radiation Therapy
Undergo EBRT

Treatment: Drugs: Isotretinoin
Given PO

Treatment: Drugs: Melphalan
Given IV

Other interventions: Sargramostim
Given SC

Treatment: Drugs: Thiotepa
Given IV

Treatment: Drugs: Topotecan
Given IV

Treatment: Drugs: Vincristine
Given IV

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Surgery
Intervention code [3] 0 0
Treatment: Drugs
Intervention code [4] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of adverse events - Assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. A one-sided Pocock group-sequential boundary with a sample size of 42 will be used to monitor the number of patients who experience at least one unacceptable toxicity during cycle 3-5 of induction. Will be assessed by the unacceptable toxicity monitoring rule and by the estimation of the combined toxic death and unacceptable toxicity rate together with a 95% confidence interval (CI).
Timepoint [1] 0 0
Up to 63 days
Primary outcome [2] 0 0
Proportion of patients who are classified as a "failure" - Feasibility "failures" are defined as patients that do not receive >= 75% of the planned dinutuximab doses during Induction. A one-sided Pocock group-sequential boundary with a sample size of 42 will be used to monitor the number of patients deemed feasibility "failures" during cycle 3-5 of induction. Will be assessed by the monitoring rule and, in addition, by estimation of the feasibility "failure" rate together with a 95% CI. The therapy will be deemed feasible at the specified dose level if the feasibility monitoring rule is not triggered.
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [1] 0 0
Response rate - Response will be determined using the revised International Neuroblastoma Response Criteria. Response rate will be calculated as the percentage of eligible patients with at least a partial response (PR) or better at the end of Induction and will also be considered in determining whether the regimen is worth further study. Will be calculated, including placement of a 95% CI on the response rate.
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [2] 0 0
Event-free survival - Kaplan-Meier curves will be generated.
Timepoint [2] 0 0
From study enrollment to the occurrence of disease relapse or progression, secondary malignancy, or death, assessed from baseline up to 5 years
Secondary outcome [3] 0 0
Overall survival - Kaplan-Meier curves will be generated.
Timepoint [3] 0 0
From study enrollment to death, assessed from baseline up to 5 years

Eligibility
Key inclusion criteria
- Patients must be enrolled on ANBL00B1 or APEC14B1 prior to enrollment on ANBL17P1.

- Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular)
verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone
marrow with elevated urinary catecholamine metabolites. The following disease groups
are eligible:

- Patients with International Neuroblastoma Risk Group (INRG) stage M disease are
eligible if found to have either of the following features:

- MYCN amplification (> 4-fold increase in MYCN signals as compared to
reference signals), regardless of age or additional biologic features; OR

- Age > 547 days regardless of biologic features;

- Patients with INRG stage MS disease with MYCN amplification

- Patients with INRG stage L2 disease with MYCN amplification

- Patients > 547 days of age initially diagnosed with INRG stage L1, L2 or MS
disease who progress to stage M without prior chemotherapy may enroll within 4
weeks of progression to stage M.

- Patients >= 365 days of age initially diagnosed with MYCN amplified INRG stage L1
disease who progress to stage M without systemic therapy may enroll within 4
weeks of progression to stage M.

- Patients initially recognized to have high-risk disease must have had no prior
systemic therapy (other than topotecan/cyclophosphamide initiated on an emergent basis
and within allowed timing as described).

- Patients observed or treated with a single cycle of chemotherapy per a low or
intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar)
for what initially appeared to be non-high risk disease but subsequently found to meet
the criteria will also be eligible.

- Patients who receive localized emergency radiation to sites of life-threatening or
function-threatening disease prior to or immediately after establishment of the
definitive diagnosis will be eligible.

- Creatinine clearance (CrCl) or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine based on age/sex as follows:

- Age 1 month to < 6 months (male 0.4 mg/dL, female 0.4 mg/dL)

- Age 6 months to < 1 year (male 0.5 mg/dL, female 0.5 mg/dL)

- Age 1 to < 2 years (male 0.6 mg/dL, female 0.6 mg/dL)

- Age 2 to < 6 years (male 0.8 mg/dL, female 0.8 mg/dL)

- Age 6 to < 10 years (male 1 mg/dL, female 1 mg/dL)

- Age 10 to < 13 years (male 1.2 mg/dL, female 1.2 mg/dL)

- Age 13 to < 16 years (male 1.5 mg/dL, female 1.4 mg/dL)

- Age >= 16 years (male 1.7 mg/dL, female 1.4 mg/dL) (within 7 days prior to
enrollment).

- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment).

- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x
ULN. For the purposes of this study, ULN for ALT is 45 IU/L (within 7 days prior to
enrollment).

- Shortening fraction of >= 27% by echocardiogram (within 7 days prior to enrollment).

- Ejection fraction of >= 50% by echocardiogram or radionuclide angiogram (within 7 days
prior to enrollment).

- No known contraindication to peripheral blood stem cell (PBSC) collection. Examples of
contraindications might be a weight or size less than the collecting institution finds
feasible, or a physical condition that would limit the ability of the child to undergo
apheresis catheter placement (if necessary) and/or the apheresis procedure.

- All patients and/or their parents or legal guardians must sign a written informed
consent.

- All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met.
Minimum age
No limit
Maximum age
30 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients >18 months of age with INRG stage L2, MYCN non-amplified, regardless of
additional biologic features.

- Patients with bone marrow failure syndromes.

- Patients that are >= 12 and =< 18 months of age with INRG stage M and all 3 favorable
biologic features (i.e., non-amplified MYCN, favorable pathology, and deoxyribonucleic
acid [DNA] index > 1) are not eligible.

- Patients on immunosuppressive medications (e.g. tacrolimus, cyclosporine,
corticosteroids for reasons other than prevention/treatment of allergic reactions,
adrenal replacement therapy, etc.) are not eligible.

- Female patients who are pregnant are ineligible since fetal toxicities and teratogenic
effects have been noted for several of the study drugs. A pregnancy test is required
for female patients of childbearing potential.

- Lactating females who plan to breastfeed their infants.

- Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method during study therapy and for two months after the last
dose of ch14.18 (dinutuximab) are not eligible.

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 0 0
Royal Children's Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
United States of America
State/province [5] 0 0
Tennessee
Country [6] 0 0
United States of America
State/province [6] 0 0
Utah
Country [7] 0 0
New Zealand
State/province [7] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Government body
Name
National Cancer Institute (NCI)
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This phase II trial studies the side effects and how well dinutuximab and sargramostim work
with combination chemotherapy in patients with high-risk neuroblastoma undergoing stem cell
transplant. Immunotherapy with monoclonal antibodies, such as dinutuximab, may induce changes
in the body's immune system and may interfere with the ability of tumor cells to grow and
spread. Sargramostim helps the body produce normal infection-fighting white blood cells.
Giving chemotherapy before a stem cell transplant, with drugs such as cisplatin, etoposide,
vincristine, doxorubicin, cyclophosphamide, thiotepa, melphalan, etoposide, carboplatin,
topotecan, and isotretinoin, helps kill any cancer cells that are in the body and helps make
room in a patient's bone marrow for new blood-forming cells (stem cells). Giving dinutuximab
and sargramostim with combination chemotherapy may work better in treating patients with
high-risk neuroblastoma undergoing stem cell transplant.
Trial website
https://clinicaltrials.gov/show/NCT03786783
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sara M Federico
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03786783